Skin is composed of the epidermis and the dermis. Below these layers lies the hypodermis, which is not usually classified as a layer of skin. The hypodermis is also commonly referred to as subcutaneous fat layer, or subcutaneous tissue. The outermost epidermis is made up of stratified squamous epithelium with an underlying basement membrane. It contains no blood vessels, and is nourished by diffusion from the dermis. The main type of cells which make up the epidermis are keratinocytes, with melanocytes and langerhans cells also present. This layer of skin is responsible for keeping water in the body and keeping other harmful chemicals and pathogens out.
The dermis lies below the epidermis and contains a number of structures including blood vessels, nerves, hair follicles, smooth muscle, glands and lymphatic tissue. The dermis (or corium) is typically 3-5 mm thick and is the major component of human skin. It is composed of a network of connective tissue, predominantly collagen fibrils providing support and elastic tissue providing flexibility. The main cell types are fibroblasts, adipocytes (fat storage) and macrophages. The hypodermis lies below the dermis. Its purpose is to attach the skin to underlying bone and muscle as well as supplying it with blood vessels and nerves. It is made up of loose connective tissue and elastin. The main cell types are fibroblasts, macrophages and adipocytes. The hypodermis contains 50% of body's fat, which serves as padding and insulation for the body. Hyaluronic acid (HA) is a part of the dermis composition and is a major component of the extra cellular matrix.
Infraorbital dark circles are a common condition that presents as a bilateral semicircle of hyperchromatic discoloration of the skin. The dark discoloration may be seen both superior and inferior to the eyelids in a semicircle shape following the orbital rim. The discoloration may extend beyond the orbital rim on both the medial and lateral sides of the eyelid opening. These dark semicircles can be a significant cosmetic problem for men and women of all ages, causing misperceptions of advanced age, sadness, tiredness, or the appearance of a hangover. This unpleasant appearance can have a significant impact on an individual's emotional well being, productivity at work or school, and overall quality of life. The presence of these dark circles may also have a negative impact on employment for individuals who rely on a positive appearance to maintain a career or develop future business.
Numerous contributing factors have been identified in the development of infraorbital dark circles, and multiple causes of the condition may be present in any one case. The very thin dermal layer beneath the eye plays an important role. Other factors that may contribute to the darkening appearance include congestion within the microvascular and subcutaneous blood vessel plexus, postinflammatory hyperpigmentation, dermal melanin deposition, allergic dermatitis, and shadowing due to edema or wrinkles. The available treatments for infraorbital dark circles, including topical creams, lotions, oils, vitamins and makeup, have limited efficacy.
Botulinum neurotoxins (BoNTs) such as, for example, BoNT/A, BoNT/B, etc., act on the nervous system by blocking the release of neurosecretory substances such as neurotransmitters. The action of BoNT is initiated by its binding to a receptor molecule on the cell surface, then the toxin-receptor complex undergoes endocytosis. Once inside the cell, BoNT cleaves exocytotic specific proteins responsible for neurotransmitter docking and release from the cell known as the SNARE proteins (soluble N-ethylmaleimide-sensitive factor attachment protein receptor). The resulting transient chemodenervation has been utilized medically to block motor neurotransmission at the neuromuscular junction leading to a variety of therapeutic applications.